CN105228666A

CN105228666A - Tissue fusion agent

Info

Publication number: CN105228666A
Application number: CN201480013056.9A
Authority: CN
Inventors: C.默克勒; E.奥德马特
Original assignee: Aesculap AG
Current assignee: Aesculap AG
Priority date: 2013-03-08
Filing date: 2014-03-05
Publication date: 2016-01-06
Anticipated expiration: 2034-03-05
Also published as: BR112015019067A2; DE102013203988A1; EP2964280A1; WO2014135566A1; EP2964280B1; US20150367042A1; US10456507B2; CN105228666B

Abstract

The present invention relates to the tissue fusion agent comprising supporting element and flocked material.In addition, the present invention relates to the surgical system comprising tissue fusion agent of the present invention and tissue fusion apparatus.In addition, the present invention relates to the method for the production of tissue fusion agent, said method comprising the steps of: a) with the coated supporting element of binding agent, and b) binding agent be moist, be adhered or stickness while, or after activated adhesive, with the supporting element flocking that flocked material is coated to binding agent.Finally, the present invention relates to the method for the production of tissue fusion agent, said method comprising the steps of: a) supporting element is changed at least partly into being adhered or stickness state, and b) with flocked material to be adhered at least partly or the supporting element of stickness carries out flocking.

Description

Tissue fusion agent

Summary of the invention

Application area and prior art

The present invention relates to tissue fusion agent (tissuefusionagent), surgical system and the method for the production of tissue fusion agent.

Tissue fusion (tissue-welding), especially coincide and the form of ligation (ligation method), by various technology implementation, and such as suturing skill and anastomosis (staplingtechnique).

Newer tissue fusion technology provides ultrasonic, the use of laser emission or heat.Reliable and the tissue fusion of safety, shortcoming is caused to be portion of tissue in corresponding circle of sensation because energy input also always degeneration occurs although implement described technology from medical science viewpoint.In some cases, this can produce ill effect to the intensity and compactness merging tissue.

WO2011/138347A2 discloses the surgical system for electrosurgery tissue fusion, it not only comprises the surgical operating instrument with 2 high frequency current electrodes (HF electrode), but also comprises the medically compatible material of supporting tissue connection.Specifically, described material can be collagen dish.

Learn from DE102009002768A1, use biocompatible materials layer as the intermediate layer between body tissue surface to be fused.

Learn from prior art, the significant drawback of tissue fusion material is that it is applied to tissue regions to be fused, described in be applied in very complicated in some cases.

Another difficulty realizes material distributing the most uniformly in tissue regions to be fused.

In addition, the possible outcome of the inhomogeneity of related materials thickness is that this material causes large change when energy input, therefore exists and does not have enough materials to provide risk that is firm and tissue fusion closely.

If use gel and liquid to realize tissue fusion, then shortcoming is that they may shift out from tissue regions to be fused in fusion process.

Problem and solution

Under this background, therefore the problem overcome by the present invention is to provide the technical solution suitably overcoming the problem mentioned when starting.

By having the tissue fusion agent of the feature of independent claims 1, by there is the surgical system of the feature of independent claims 15 and solving this problem by the production method of the feature with independent claims 16 and 17.The preferred embodiment of tissue fusion agent is defined in dependent claims 2-14.The word that all authority requires forms content of the present invention hereby by specific reference.

First aspect, the present invention proposes tissue fusion agent, namely for organizing the fusion of (being generally body tissue) or connection or closed agent.

Tissue fusion agent comprises supporting element (supportingelement) and flocked material (flockmaterial).

Tissue fusion agent of the present invention has following advantage:

Due to the existence of flocked material, tissue fusion agent generally speaking has the surface area of expansion, makes it to set up with tissue regions to be fused the contact improved, and is improve with regard to described contact the with regard to compactness of the intensity about fusion to be achieved.

In addition, the tissue fusion agent comprising flocked material provides other material, ensure that to provide after being applied to tissue regions to be fused enough materials for strong, specifically closely, the tissue fusion of fine and close and infiltration.

Another advantage relevant with the surface area expanded caused by flocked material is that supporting element can be thinner, and therefore more has flexibility, but provides enough material strong to realize, specifically closely, the tissue fusion of fine and close and infiltration.

Another advantage is compared with versatile material, caused by the surface area that it expands (due to flocked material existence caused by) tissue fusion agent can evenly, be specifically applied to tissue regions to be fused in the mode of more homogenizing.Therefore, any inhomogeneity in supporting element thickness can by more effective payment in fusion process.

In addition, the surface area of the tissue fusion agent of expansion especially advantageously allows to cover tissue regions to be fused completely, and without the need to before tissue fusion process or period make tissue fusion agent complicated be adapted to the ratio of tissue regions to be fused that needs.

But, may advantageously carry out indication specificity adaptation (indication-specificadaptation), the form of (punch-out) is such as got with punching, to make tissue fusion agent and housing construction to be anastomosed (such as vessel sections, intestinal section, lymphatic vessel section or nervous pathway section) match, more particularly match with its wall thickness.

By supporting element and/or the material of flocked material and/or the concrete selection of additive, another likely impact or regulate the Fusogenic properties of tissue fusion agent clearly, the melting capacity of such as tissue fusion agent, adhesive and/or conduction or impedance behavior and absorbent properties.This not only allows the fusion process specificity of tissue fusion agent but also allows the indication specificity of tissue fusion agent to adapt to.Therefore, such as may guarantee the absorption of tissue fusion agent and thus guarantee cell, extracellular matrix or be organized in the complete growth that district is organized in whole fusion.

Shortening fusion process is particularly advantageously facilitated in above-listed aspect, and therefore shorten possible energy input (if using the comparatively new organization integration technology mentioned when starting), therefore tissue fusion agent of the present invention generally speaking also allows to carry out the fusion to organizing milder.

Compare with liquid agent with gel, the dislocation risk during the advantage of tissue fusion agent is fusion process is quite low.

In a word, tissue fusion agent make to carry out simple, can reproduce and be particularly conducive to the tissue fusion process of wound healing.

In the present case, state " supporting element " and be generally understood as the substrate or holder that refer to flocked material.

In the present case, term " flocked material " is appreciated that as referring to by flocking technology, preferably uses binding agent to be applied to the material on supporting element or supporting element surface.Generally speaking, material is the fiber (will mention preferred fibre length below) of regulation fibre length, and it is generally by by ultimate fibre (such as extruding fiber), more particularly cut to cut or grind to fall apart produce by the so-called long fibre section of being trimmed to (trimmingtolength), more particularly.

In a preferred embodiment, therefore tissue fusion agent also comprises adhesive layer.

Adhesive layer be substantially coated on serially supporting element or its on the surface, namely spread all on whole surface.

But, according to the present invention, when adhesive layer only part or on subregion coated supporting element or supporting element surface time be preferred.

Specifically, the offside of the supporting element that the present invention can provide bonded layer coated, the more particularly corresponding main surfaces (mainsurface) of the supporting element that bonded layer is coated.

In the present case, term " first type surface " is appreciated that as referring to the face with the supporting element that maximized surface amasss.

The thickness of adhesive layer can be 1 μm-500 μm, more particularly 3 μm-300 μm, preferably 5 μm-100 μm.

Flocked material is preferably connected with adhesive layer.More particularly, flocked material is connected by the surface of adhesive layer with supporting element or supporting element.For this reason, flocked material is general partly, more particularly only partly infiltrates adhesive layer.But flocked material does not preferably infiltrate supporting element.

Flocked material is to infiltrate adhesive layer based on the length of the 0.5%-95% of its total length, more particularly 3%-50%, preferably 5%-20%.

Adhesive layer preferably exists as nonwoven layer or coating.Such as, adhesive layer can be used as coating or last one deck covers with paint, lacquer, colour wash, etc. (finish), thin film, gel more particularly as the formation such as hydrogel, paste.

In still another embodiment, with tissue fusion agent total weight, adhesive layer forms the ratio of 0.1% weight-90% weight, more particularly 0.5% weight-50% weight, preferably 1% weight-25% weight.

It is useful for for adhesive layer, comprising biocompatible materials or being formed by this kind of material.

Preferred adhesive layer comprises can absorbing material or formed by this kind of material again.

The material described in nearest two embodiments is preferably polymer, is more particularly copolymer.

In the present case, term " copolymer " is appreciated that as referring to the polymer comprising at least two kinds of different monomeric units.Therefore, term " copolymer " is not only included in compared with the copolymer in narrower sense, i.e. so-called bipolymer (comprising the copolymer of two kinds of different monomeric units), but also comprises terpolymer, quadripolymer etc.Copolymer can be selected from random copolymer, alternate copolymer, block copolymer or segmented copolymer, graft copolymer and mixture in addition, is more particularly selected from its blend.

Preferred adhesive layer comprises can absorbing material or by being formed by absorbing material more again, describedly can be selected from polyhydroxyalkanoatefrom, protein, exoprotein, serum proteins, polysaccharide, mucopolysaccharide, the polysaccharide with carboxyl, the polysaccharide with amino, the polysaccharide with aldehyde radical, its copolymer, its salt, its stereoisomer by absorbing material again, more particularly its diastereomer and mixture, more particularly its blend.

More particularly, adhesive layer can comprise can absorbing material or can by being formed by absorbing material more again, describedly can be selected from polyglycolic acid or polyglycolide by absorbing material again, polylactic acid or polylactide, Ju diethyleno dioxide ketone, polytrimethylene carbonate, poly-6-caprolactone, poly-3-hydroxybutyrate or poly-3-hydroxybutyrate ester, poly-4 hydroxybutyric acid or poly-4 hydroxybutyric acid ester, polysaccharide, cellulose, cellulose derivative, alkylcellulose, methylcellulose, hydroxy alkyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxyalkyl cellulose, carboxymethyl cellulose, starch, amylose, amylopectin, glucosan, dextrin, chitin, chitosan, hyaluronic acid, dextran sulfate, heparin, Heparan sulfate, chondroitin sulfate, dermatan sulfate, collagen, gelatin, elastin laminin, reticulin, fibronectin, laminin，LN, fibrin, fibrinogen, albumin, its copolymer, its salt and composition thereof, more particularly its blend.

In an alternate embodiment, flocked material is directly connected (namely without adhesive layer) with the surface of supporting element or supporting element.For this reason, flocked material generally infiltrates supporting element.Such as, flocked material can infiltrate supporting element in the length based on the 0.5%-95% of its total length, more particularly 3%-50%, preferably 5%-20%.

Supporting element is preferably formed as the plane of flattening, more particularly two dimension or the three-dimensional plane of flattening.

Specifically, supporting element can layering or in synusia (synusia of material), thin film, thin slice, film, dish etc. form.

Preferred supporting element is dish type, more particularly in avette, circular or the form of oblong-shaped disc or the form in noncircular pad, and the form preferably in thin slice.

In particularly preferred embodiments, supporting element is annular or substantially annular.

Specifically, supporting element can annulus form exist, its ring width is equivalent to or is substantially equivalent to the housing construction of (anastomize) to be anastomosed, specifically the wall thickness of such as vessel sections, intestinal section, lymphatic vessel section and/or nervous pathway section.

In order to accelerate the absorption of tissue fusion agent, in further embodiment, supporting element may comprise hole, perforation, punching etc.

In addition, the thickness of supporting element can be 1 μm of-5mm, more particularly 2 μm of-2mm, preferably 20 μm of-1mm.

In still another embodiment, supporting element comprises two or more supporting element layers, preferably two supporting element layers.

Supporting element layer by non-flocking side, be connected to each other more particularly by first type surface, preferably adhesively combines.Flocked material is preferably arranged on those opposite sides of the side of the supporting element layer be connected to each other.

In useful embodiment, supporting element comprises coagulated material and/or hot-melt adhesive material or is formed by this kind of material.

More particularly, supporting element is fusible material under being included in the impact of high-frequency alternating current (HF electric current), hot, ultrasonic and/or laser emission or is formed by this kind of material.

It is under the impact of the alternating current of 200kHz-4000kHz, more particularly 100kHz-600kHz, preferably 250kHz-500kHz be fusible material or formed by this kind of material that preferred supporting element is included in frequency.

Particularly preferably comprise can absorbing material or formed by this kind of material again for supporting element.Which ensure that cell, extracellular matrix or be organized in whole supporting element and grow, make it the raising (compared with not using the tissue fusion of tissue fusion agent of the present invention) that may realize aggregation strength.

In still another embodiment, the material for supporting element described in foregoing embodiments can be synthetic source, biogenic and/or restructuring source.

As alternative or in addition, the material of supporting element can be natural source or natural source.Specifically, material can be xenogenesis source, preferred pig, cattle and/or Ma Yuan.Or the material of supporting element also can be people source.

The material of preferred supporting element is polymer, is more particularly be selected from following polymer: synthetic polymer, recombinant polymers, naturally occurring polymer or biopolymer and composition thereof, more particularly its blend.

Preferred supporting element comprises can absorbing material or formed by this kind of material again, describedly can be selected from polyhydroxyalkanoatefrom, protein, exoprotein, serum proteins, polysaccharide, mucopolysaccharide, the polysaccharide with carboxyl, the polysaccharide with amino, the polysaccharide with aldehyde radical, its copolymer, its salt, its stereoisomer by absorbing material again, more particularly its diastereomer and mixture, more particularly its blend.

More particularly, supporting element can comprise can absorbing material or can be formed by this kind of material again, describedly can be selected from polyglycolide or polyglycolic acid by absorbing material again, polylactide or polylactic acid, Ju diethyleno dioxide ketone, poly-3-hydroxybutyrate ester or poly-3-hydroxybutyrate, poly-4 hydroxybutyric acid ester or poly-4 hydroxybutyric acid, polytrimethylene carbonate, poly-6-caprolactone, polyvinyl alcohol, cotton, cellulose, cellulose derivative is alkylcellulose such as, methylcellulose, hydroxy alkyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxyalkyl cellulose, carboxymethyl cellulose, starch, amylose, amylopectin, glucosan, dextrin, chitin, chitosan, hyaluronic acid, dextran sulfate, heparin, Heparan sulfate, chondroitin sulfate, dermatan sulfate, collagen, gelatin, elastin laminin, reticulin, fibronectin, laminin，LN, fibrin, fibrinogen, albumin, its copolymer, its salt, stereoisomer, more particularly its diastereomer and mixture, more particularly its blend.

In still another embodiment, supporting element comprises Polyethylene Glycol or is formed by Polyethylene Glycol.

In still another embodiment, supporting element can comprise fusing point lower than 100 DEG C, and specifically fusing point is the material of 70 DEG C-90 DEG C or can be formed by this kind of material.

In still another embodiment, flocked material can be microgranule flocked material and/or fibre flocking material can be maybe flocked fiber.

In still another embodiment, microgranule flocked material and/or fibre flocking material can grind the existence of loose form.

More particularly, microgranule flocked material and/or fibre flocking material can be mill staple in bulks, are more particularly mill scattered planting Down Fiber.

Substantially, microgranule flocked material can the form of powder or pellet exist.

Such as, the particle diameter of microgranule flocked material or particle diameter can be 0.05 μm of-5mm, more particularly 0.1 μm of-3mm, preferably 10 μm of-2mm.

Particularly preferably fibre flocking material is with flocked fiber, more particularly exist with the form of monofilament flocked fiber.

Fibre flocking material can be made in addition to have and/or not have texture.

Optimum fiber flocked material has all even fibre length determined.

The fibre length of fibre flocking material can be 40 μm of-15mm substantially, more particularly 50 μm of-10mm, preferably 100 μm of-5.0mm.More particularly, the fibre length of fibre flocking material can be 10 μm of-5mm, more particularly 40 μm of-4mm, preferably 50 μm of-3mm, more preferably 100 μm of-2mm.Particularly preferably the fibre length of fibre flocking material can be 100 μm of-3mm, preferably 200 μm of-2mm.

In addition, the fiber thickness of fibre flocking material or fibre diameter can be 5 μm-800 μm, more particularly 7 μm-300 μm, preferably 10 μm-150 μm.

In addition, the line density of fibre flocking material can be 0.01dtex-1000dtex, more particularly 0.1dtex-500dtex, preferred 0.3dtex-200dtex.Specifically, the line density of fibre flocking material can be 0.1dtex-50dtex, preferred 0.9dtex-22dtex, more preferably 1dtex-10dtex.Tolerance " dtex " (dtex (decitex)) means the line density of 1g/10000m fibre flocking length of material.

In still another embodiment, flocked material can from supporting element or from supporting element surface or cover the length that the adhesive layer on supporting element surface extends over 10 μm of-5mm, more particularly 40 μm of-4mm, preferably 50 μm of-3mm.

In still another embodiment, flocked material can be arranged in two offsides of supporting element, more particularly in two corresponding main surfaces of supporting element, or from two offsides of supporting element, more particularly stretch out from two corresponding main surfaces of supporting element.

In still another embodiment, flocked material perpendicular to or be basically perpendicular to the surface alignment of supporting element or supporting element.Term " substantially vertical " can comprise and to deviate to many 5 ° from right angle.

In alternate embodiment, flocked material is with the surperficial bevel arrangement relative to supporting element or supporting element, and oblique angle is greater than 0 °, but is less than 85 °.

In still another embodiment, flocked material can the density array of 1%-30%, more particularly 5%-25%, preferably 10%-20% on the surface of supporting element or supporting element.

In still another embodiment, flocked material take density as 1-2000 granule and/or fiber/mm ², more particularly 5-1000 granule and/or fiber/mm ², preferably 10-500 granule and/or fiber/mm ²granule and/or the form of fiber be arranged on the surface of supporting element or supporting element.

In addition, flocked material can in a pattern or be arranged in irregular or random mode on the surface of supporting element or supporting element.

Such as, flocked material can linear array, classification arrangement (graduatedarrangement), helical arrangement or helical arrangement, bend alignment, arrangement of wriggling, sinusoidal arrangement, annular array and combination thereof form be arranged on the surface of supporting element or supporting element.

According to the present invention, for flocked material, the surface being arranged in supporting element or supporting element with the pattern of the cross section being such as equivalent to housing construction to be anastomosed may be preferred, and the cross section of described housing construction to be anastomosed is as vessel sections, intestinal section, lymphatic vessel section, nervous pathway section etc.Therefore, for flocked material, with avette, more particularly circular, preferred circular pattern or to be arranged in supporting element with oval pattern may be preferred on the surface.

In addition, fibre flocking material can have circular cross section or non-circular cross sections, more particularly has avette, oval, polygonal as triangle, rectangle, square, trhomboid, pentagon, hexagon and/or star-shaped cross-section.

In addition, with tissue fusion agent total weight, the flocked material content of tissue fusion agent can be 0.01% weight-50% weight, more particularly 0.5% weight-20% weight, preferably 1.0% weight-10% weight.

In a useful embodiment, flocked material comprises coagulated material and/or hot-melt adhesive material or is formed by this kind of material.

More particularly, flocked material is fusible material under being included in the impact of high-frequency alternating current (HF electric current), hot, ultrasonic and/or laser emission or is formed by this kind of material.

It is under the impact of the alternating current of 200kHz-4000kHz, more particularly 100kHz-600kHz, preferably 250kHz-500kHz be fusible material or formed by this kind of material that preferred flocked material is included in frequency.

Particularly preferably comprise can absorbing material or formed by this kind of material again for flocked material.

In still another embodiment, what describe in foregoing embodiments can be synthetic source, biogenic and/or restructuring source for flocked material material.

As alternative or in addition, the material of flocked material can be natural source or natural source.Specifically, material can be xenogenesis source, preferred pig, cattle and/or Ma Yuan.As alternative or in addition, the material of flocked material can be people source.In these embodiments, flocked material preferably exists as mill scattered planting down material.

The material of preferred flocked material is polymer, is more particularly copolymer.Specifically, polymer can be selected from synthetic polymer, recombinant polymers, naturally occurring polymer or biopolymer, its copolymer and mixture, more particularly its blend.

Preferred flocked material comprises can absorbing material or formed by this kind of material again, describedly can be selected from polyhydroxyalkanoatefrom, protein, exoprotein, serum proteins, polysaccharide, mucopolysaccharide, the polysaccharide with carboxyl, the polysaccharide with amino, the polysaccharide with aldehyde radical, its copolymer, its salt, its stereoisomer by absorbing material again, more particularly its diastereomer and mixture, more particularly its blend.

More particularly, flocked material can comprise can absorbing material or can be formed by this kind of material again, describedly can be selected from polyglycolide or polyglycolic acid by absorbing material again, polylactide or polylactic acid, Ju diethyleno dioxide ketone, poly-3-hydroxybutyrate ester or poly-3-hydroxybutyrate, poly-4 hydroxybutyric acid ester or poly-4 hydroxybutyric acid, polytrimethylene carbonate, poly-6-caprolactone, polyvinyl alcohol, cotton, cellulose, cellulose derivative is alkylcellulose such as, methylcellulose, hydroxy alkyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxyalkyl cellulose, carboxymethyl cellulose, starch, amylose, amylopectin, glucosan, dextrin, chitin, chitosan, hyaluronic acid, dextran sulfate, heparin, Heparan sulfate, chondroitin sulfate, dermatan sulfate, collagen, gelatin, elastin laminin, reticulin, fibronectin, laminin，LN, fibrin, fibrinogen, albumin, its copolymer, its salt, stereoisomer, more particularly its diastereomer and mixture, more particularly its blend.

In still another embodiment, flocked material comprises Polyethylene Glycol or is formed by Polyethylene Glycol.

In still another embodiment, flocked material can comprise fusing point is the material of 70 DEG C-90 DEG C lower than 100 DEG C, specifically fusing point or can be formed by this kind of material.

According to the present invention, it may be preferred further for existing with the form comprising the mixture of different flocked material for flocked material.In this case, flocked material can be different from each other with regard to following parameter with regard to being selected from: particle diameter (when microgranule flocked material), fibre length (at fibre flocking material), thickness or diameter, line density (at fibre flocking material) and/or material.With regard to the parameter that this section is mentioned, up to the present carry out fully quoting (fullreferenceismadetothedescriptionsofar) to described description.

In still another embodiment, supporting element and flocked material can comprise identical material or can be formed by identical material.Or supporting element and flocked material can comprise different materials or can be formed by different materials.With regard to possible material, up to the present carry out fully quoting to described description.

In favourable embodiment, to tissue fusion agent, more particularly additive be can add in supporting element and/or flocked material, one or optional multiple additives namely comprised.

Improving or impedance reduction to realize electrical conductivity, the raising electrical conductivity of the form preferably in salt can be contained or fall the tissue fusion agent of low-impedance additive, more particularly supporting element and/or flocked material by providing package.

Improve electrical conductivity or fall low-impedance additive and be preferably selected from alkali halide, alkaline-earth halide, phosphate, alkali metal phosphate, alkali earth metal phosphate, its mixed phosphate and composition thereof.

Such as, improve electrical conductivity or fall low-impedance additive and can be selected from sodium chloride, potassium chloride, barium chloride, magnesium chloride, calcium chloride, sodium phosphate, potassium phosphate, barium phosphate, magnesium phosphate, calcium phosphate, its mixed phosphate and composition thereof.

In still another embodiment, improving electrical conductivity or fall low-impedance additive can comprise with tissue fusion agent total weight, more particularly to support the ratio of total weight 0.1% weight-20% weight, more particularly 0.1% weight-10% weight, preferably 0.8% weight-5% weight of thin slice and/or flocked material.

In alternate embodiment, flocked material comprises the additive of the reduction electrical conductivity preferably in metallic forms, and described metal is such as selected from aluminum, ferrum, silver, zinc, magnesium and mixture, is more particularly its alloy.

In order to realize biology, materia medica and/or medicine effect, can at providing package in alternative or other embodiments containing the tissue fusion agent being selected from following active component, more particularly supporting element and/or flocked material: bioactive ingredients, active constituents of medicine, medicinal active ingredient and composition thereof.

In still another embodiment, tissue fusion agent, more particularly supporting element and/or flocked material can comprise and be selected from following active component: antimicrobial is antibiotic more particularly, active component, wound healing promoting active component, antimicrobial activity composition, anti-inflammatory active ingredient, procoagulant activity composition, somatomedin, cell differentiation factor, cell adhesion molecules, the recruiting cells factor, cell receptor, the Cell binding factor, cytokine, peptide, structural protein, exoprotein is collagen such as, serum proteins are albumin such as, polysaccharide is hyaluronic acid such as, oligonucleotide, polynucleotide, DNA, RNA, its salt, stereoisomer, more particularly its diastereomer and composition thereof.

Such as, tissue fusion agent, more particularly supporting element and/or flocked material can comprise and be selected from following active component: biguanide, poly hexamethylene biguanide (PHMB), triclosan, chlorhexidine, gentamycin, vitamin, copper, zinc, silver, gold, its salt, its stereoisomer, more particularly its diastereomer and composition thereof.

In order to improve tissue fusion agent, the more particularly stability of supporting element and/or flocked material, can provide the tissue fusion agent existed with cross-linked form, more particularly supporting element and/or flocked material in still another embodiment.Tissue fusion agent, more particularly supporting element and/or flocked material can be physics and/or chemical crosslinking.Tissue fusion agent, more particularly the physical crosslinking of supporting element and/or flocked material realizes by such as suitable irradiation technique.Chemical crosslinking generally realizes by suitable chemical cross-linking agent.

Such as, tissue fusion agent, more particularly supporting element and/or flocked material can use be selected from following chemical cross-linking agent be cross-linked: aldehyde such as formaldehyde, dialdehyde such as glutaraldehyde, polyacetals such as dextran aldehyde, carbodiimide, vulcabond such as hexamethylene diisocyanate, its salt and composition thereof.

In still another embodiment, tissue fusion agent the form of supporting element and flocked material can exist or be made up of supporting element and flocked material, and it is possible for optionally adding additive to supporting element and/or flocked material.With regard to the more multiple features of supporting element and flocked material and advantage, up to the present carry out fully quoting to described description.

Tissue fusion agent of the present invention is preferably surgical tissue fusion agent.

Tissue fusion agent is generally suitable for closing, closing or airtight biological tissue, more particularly people and/or animal tissue.Therefore, specifically, tissue fusion agent of the present invention can play occlusive agent.

In particularly preferred embodiments, tissue fusion agent expection is used for carrying out coincideing and/or ligation.Specifically, to coincide can be end to end anastomosis, side coincide, end-to-side anastomosis and side to side anastomosis.In addition, coincide and can be selected from vascular anastomosis, more particularly blood vessel and/or lymphatic vessel coincide, Surgical healing and neural anastomosis.

In addition, such as, when organ, tissue fusion agent can be expected for tissue closure or organize airtight, especially after excision, preferably postoperative at Partial Resection.

Preferred application relates to using-system fusion agent in the electrosurgery carrying out body tissue merges in addition.

In useful embodiment, tissue fusion agent exists with sterile form, specifically exists with final product form.Such as, the sterilizing of tissue fusion agent can use oxirane to realize.

Second aspect, the invention provides the surgical system comprising tissue fusion agent of the present invention and tissue fusion apparatus.Tissue fusion apparatus preferably comprises at least two electrodes for releasing or input current, more particularly high frequency electric (HF electric current).Or tissue fusion apparatus can be laser apparatus or for generation of hyperacoustic apparatus.

But surgical system is preferably electrosurgical operation system, it comprises tissue fusion agent of the present invention and for releasing or at least two electrodes of input current, more particularly high frequency electric (HF electric current).Preferably two electrodes are the assemblies of the operating theater instruments with two tool elements, described tool elements is one of moveable and each self-contained two electrodes toward each other, described electrode is preferably on the converged position of tool elements, limit minimum range each other, be positioned at opposite face each other and facing with each other.Relevant this kind of surgical operating instrument, with reference to WO2011/138347A2, it is quoted when starting, and in this, make its complete disclosure become the content of this description.

This surgical system relevant, the more multiple features of especially tissue fusion agent, supporting element and/or flocked material and advantage, up to the present carried out fully quoting to described description.

The third aspect, the invention provides and produce tissue fusion agent, more particularly produce the method for the tissue fusion agent described in the text of first aspect present invention, said method comprising the steps of:

A) with the coated supporting element of binding agent, and

B) binding agent be moist, be adhered or stickness while, or after activated adhesive, with the supporting element flocking that flocked material is coated to binding agent.

In the present case, term " flocking " is appreciated that as referring to flocked material, the form especially in fiber, is coated on the technology on the adhesive layer on supporting element or (at least partly) coated supporting element or supporting element surface.

In the present case, term " activation " or " activation " should comprise and make it to give binding agent humidity, be adhered or the technology of stickness.Corresponding technology can be selected from fusing, liquefaction, moistening, soaks, floods, heats, irradiates, ultrasound wave produces, chemicals uses and combination.

Undertaken by such as following with the coated supporting element of binding agent or its surface: extrude, inject, cast, silk screen printing, flood, soak, spray, sprawl, blade is coated with and/or rolling techniques.

Specifically, above-mentioned coating technology depends on the concrete binding agent used.

Formed by this kind of material if binding agent comprises such as fusible material or binding agent, then by extrusion technology described binding agent is coated on supporting element or its on the surface.

By contrast, if binding agent exists as waterborne liquid, more particularly exist as aqueous solution, then by dipping, spray or technology of sprawling binding agent is preferably applied in supporting element or its on the surface.

If binding agent exists as paste or gel, more particularly exist as hydrogel, then by brushing, sprawling, blade coating, roll extrusion etc. advantageously binding agent is applied in supporting element or its on the surface.

Supporting element or its surface are substantially by scattering technology, spray technique, blown technique, vibrotechnique and/or electrostatic technique flocking.

Preferably by electrostatic spinning, flocking is carried out to supporting element or its surface.

When electrostatic spinning, flocked material is applied in the electric field on the adhesive layer on supporting element or coated supporting element or its surface.

In useful embodiment, electrostatic spinning carries out in flocking plant.Flocking plant generally receives negative charge, and the general ground connection of supporting element.Therefore, flocked material is usually with the adhesive layer on vertical or substantially vertical mode " directive " supporting element or coated supporting element or its surface.

Highly accelerate because flocked material in the electric field experienced by, therefore flocked material well infiltrates supporting element or adhesive layer is generally achieved.

In preferred embodiments, supporting element as electrode, more particularly ground electrode with to electrode, more particularly high-field electrode uses together.Particularly preferably supporting element is used as negative electrode, and to electrode, preferred high-field electrode is used as anode.

Distance between electrode (supporting element and to electrode) can be 2cm-200cm, more particularly 5cm-100cm, preferred 7cm-50cm.

In addition, in order to carry out electrostatic spinning, the voltage of 5kV (kilovolt)-120kV (kilovolt), more particularly 10kV (kilovolt)-100kV (kilovolt), preferably 20kV (kilovolt)-80kV (kilovolt) can be applied in-between the electrodes.

Relevant foregoing embodiments, the more multiple features of method described in especially tissue fusion agent, supporting element and/or flocked material and advantage, up to the present carried out fully quoting to described description.

Fourth aspect, the present invention proposes the alternative approach for generation of the tissue fusion agent described in the text of tissue fusion agent, more particularly first aspect present invention.Described method comprises the following steps:

A) supporting element is changed into be at least partly adhered or stickness state, and

B) with flocked material to be adhered at least partly or the supporting element of stickness carries out flocking.

Such as, by fusing, liquefaction, moistening, soak, flood, heat, irradiate, ultrasound wave produces, chemicals uses or its combination, supporting element is changed into and is adhered at least partly or stickness state.

In useful embodiment, only partly supporting element is changed into and be adhered or stickness state.

Preferably one or more surface layers of supporting element are changed into and be adhered or stickness state.

Relevant the method, the more multiple features of especially tissue fusion agent, supporting element and/or flocked material and advantage, up to the present carried out fully quoting to described description equally.

By the following description of the preferred embodiment in exemplary form, disclose more multiple features of the present invention and advantage.In all cases, each feature can realize by oneself or in combination with each other.Preferred embodiment is only served and is set forth the present invention further, and for understanding the present invention better, and do not limit the invention to this.

Exemplary

1. the production of flocked fiber

Use extruding device, squeeze out the fiber comprising collagen, be trimmed to the length of 100 μm subsequently to form flocked fiber.

2. pair support thin slice comprising polyglycolide carries out flocking

By by the high voltage applications of 60kV on one of two first type surface, in the flocking storehouse with the collagen flocked fiber produced in 1, to comprising polyglycolide and carrying out flocking with the support thin slice that still adhesive layer that is moist or that be adhered is coated.

After adhesive layer ripening, with corresponding manner collagen flocked fiber to supporting that the corresponding main surfaces of thin slice carries out flocking.

Subsequently, by the tissue fusion agent packaging so obtained, and ethylene oxide sterilizing is used.

3. pair polyglycolide supporting element comprising two support thin slices carries out flocking

Subsequently, with corresponding manner, with collagen flocked fiber to same to be made up of polyglycolide and have equally still moist or be adhered second of adhesive layer support that thin slice carries out flocking.

Afterwards, support that thin slice is adhered combination each other along its non-flocking first type surface by two.

4. pair support thin film comprising poly-(6-caprolactone-propylene carbonate) copolymer carries out flocking

Use extruding device, produce and comprise the fiber of poly-(6-caprolactone-propylene carbonate) copolymer, use accurate cutting device to be trimmed to subsequently flocked fiber that length is 100 μm.

Subsequently flocked fiber is soaked in the chloride containing calcium water-bath with the salt improving electrical conductivity.

To take out from water-bath and after drying subsequently, by using electric field, flocked fiber is being applied in and comprises poly-(6-caprolactone-propylene carbonate) copolymer and thickness is on two first type surfaces of the thin film of 200 μm.Binding agent for being connected with support thin film by flocked fiber is the film surface melted by infra-red radiation.

From the support thin film of flocking thus, go out ring segment subsequently, its ring width is equivalent to the wall thickness of different intestinal section.

5. pair support thin film comprising polyvinyl alcohol carries out flocking

Comprise polyvinyl alcohol and the thickness support thin film that is 200 μm with comprising albuminous flocked fiber (fibre length 100 μm) flocking on its both first type surface.

Adhesive therefor is the film surface that water (sprayed-onwater) by spraying gives stickness.

After flocking operations, by the support film drying of thus obtained flocking.

6. carry out anastomosis of bowel

In animal (pig), excision is carried out when small intestinal.Subsequently, the distal small intestine of gained is in parallel to each other, and by two otch, two arm HF apparatuses is introduced in intestinal.

When two apparatus arms are combined, will in the form of support thin slice be made up of polyglycolide and fusion site is introduced in the tissue fusion agent that side length is the collagen fiber flocking of 5mm.At this, collagen fiber inwardly point to fusion site.

When carrying out tissue fusion, collagen fiber melt and and tissue-welding.Support that thin slice melts equally, and carry out other airtight (in " condensation " mode) fusion is outside.

Finally, cut between coincideing, and then produce continuous print chamber in tissue fusion district.After cut closure (by sewing up or upgrading fusion (renewedfusion)), operation terminates.

Claims

1. a tissue fusion agent, it comprises supporting element and flocked material.

2. the tissue fusion agent of claim 1, is characterized in that described flocked material is connected with supporting element by adhesive layer.

3. 1 or 2 tissue fusion agent of claim, it is characterized in that described supporting element as the plane of flattening, the preferred two-dimentional plane of flattening, more particularly with dish form formed.

4. the tissue fusion agent any one of aforementioned claim, is characterized in that described supporting element is the form of thin slice.

5. the tissue fusion agent any one of claim 1-3, is characterized in that the rounded dish of described supporting element, is more particularly the form of annular disk.

6. the tissue fusion agent any one of aforementioned claim, is characterized in that described flocked material exists with the form of flocked fiber, preferably monofilament flocked fiber.

7. the tissue fusion agent any one of claim 1-5, is characterized in that described flocked material is with the form of microgranule flocked material, more particularly with the form existence of powder or pellet.

8. the tissue fusion agent any one of aforementioned claim, it is characterized in that described supporting element and/or flocked material comprise can absorbing material or be made up of this kind of material again, describedly can be preferably selected from polyhydroxyalkanoatefrom, polyvinyl alcohol, protein, exoprotein, serum proteins, polysaccharide, mucopolysaccharide, the polysaccharide with carboxyl, the polysaccharide with amino, the polysaccharide with aldehyde radical, its copolymer, its salt, stereoisomer by absorbing material again, more particularly its diastereomer and mixture, more particularly its blend.

9. the tissue fusion agent any one of aforementioned claim, is characterized in that described tissue fusion agent, more particularly described supporting element and/or flocked material comprise the raising electrical conductivity of the form preferably in salt or fall low-impedance additive.

10. the tissue fusion agent of claim 9, is characterized in that described raising electrical conductivity or falls low-impedance additive being selected from alkali halide, alkaline-earth halide, phosphate, alkali metal phosphate, alkali earth metal phosphate, mixed phosphate and composition thereof.

Tissue fusion agent any one of 11. claim 1-8, is characterized in that described tissue fusion agent, more particularly described supporting element and/or described flocked material comprise the additive reducing electrical conductivity, preferably in metallic forms.

Tissue fusion agent any one of 12. aforementioned claim, is characterized in that described tissue fusion agent, more particularly described supporting element and/or flocked material comprise and is selected from following active component: bioactive ingredients, active constituents of medicine, medicinal active ingredient and composition thereof.

Tissue fusion agent any one of 13. aforementioned claim is such as when organ, especially after excision, preferably postoperative as surgical tissue fusion agent at Partial Resection, is preferred for carrying out coincideing and/or ligation and/or tissue closure.

Tissue fusion agent any one of 14. aforementioned claim, it merges for body tissue electrosurgery.

15. 1 kinds of surgical systems, it comprises tissue fusion agent any one of aforementioned claim and tissue fusion apparatus, and described apparatus preferably includes for releasing or at least two electrodes of input current, more particularly high frequency electric (HF electric current).

16. 1 kinds of organization of production fusion agents, the method for the especially tissue fusion agent of claim 1-14, said method comprising the steps of:

A) with the coated supporting element of binding agent, and

The method of 17. 1 kinds of organization of production fusion agents, the especially tissue fusion agent of any one of claim 1-14, said method comprising the steps of: